Kinase is a class of important phosphotransferases whose function is to catalyze the transfer of the γ-phosphate group at the end of adenosine triphosphate to the amino acid residues of a particular substrate protein to phosphorylate the protein and thereby play its physiological biochemical function. Protein kinases are key components of cellular signal transduction pathways. Protein kinases are involved in the regulation of multiple cellular processes, including cell growth, energy metabolism, cell cycle, transcription, apoptosis, differentiation and so on. In addition, protein kinases play a vital role in maintaining intercellular relationships, homeostasis, immune system function and so on. The abnormal regulation of protein kinases is associated with the development of various diseases, especially tumors. Kinase has become important targets for disease treatment, it has attracted wide attention.
Since 2001 the first tyrosine protein kinase drug imatinib (Imatinib) listed, protein kinase drugs have become the fastest growing unit in the global drug market. As of 2014, more than 20 protein kinase drugs have been approved worldwide, including more than 10 antitumor drugs, such as Imatinib, Gefitinib, Erlotinib, Sorafenib, Sunitinib, Dasatinib, Nilotinib, Laptinib, Pazopanib, and Regorafenib. The successful development of protein kinases, especially the development of anti-tumor drugs targeting multiple protein kinases, has made it a hot research field for the scientific and pharmaceutical industry.
Although current research and development of protein-kinase drug has achieved great success, there is still a lot of room and potential for development. In particular, the development of novel protein kinase inhibitors for the treatment of refractory tumors, drug-resistant tumors, and highly metastatic tumors, such as triple-negative breast cancer, drug-resistant lung cancer, liver cancer, pancreatic cancer, melanoma, multiple leukemia and so on, is still the current research hotspot.